Deciphering the role of CD29 for tumor cell invasion and liver metastasis in small cell lung cancer

Small cell lung cancer (SCLC) represents with ~15 % of cases the most aggressive form of lung cancer and can arise as primary or secondary SCLC from neuroendocrine or non-neuroendocrine precursors. SCLC is in general characterized by a rapid tumor growth with extremely poor outcome, due to rapid recurrence after standard chemo- or chemo-immunotherapy and due to early formation of metastasis. However, so far, the molecular mechanism that induces tumor cell invasion and the formation of SCLC metastasis remains largely elusive.

The extracellular matrix (ECM) is a highly dynamic network of extracellular proteins, proteoglycans and glycoproteins. Integrins are transmembrane receptors that enable cell-ECM-adhesion and tumors actively remodel the communication with the ECM to promote tumorigenesis and metastatic spread.

The Angiopoietin-2 (ANG-2)/CD29 (Integrin β1/ITGB1)-dependent signaling axis induces epithelial-to-mesenchymal transition and regulates focal adhesion kinase signaling in metastatic processes. Particularly in SCLC, CD29 contributes to liver metastasis formation. Our goal is to decipher the therapeutic value of ANG-2/CD29 blockade in preclinical models and ultimately improve the treatment of SCLC patients by reducing metastatic burden.